ERK1/2信号通路对缺血后适应大鼠皮层的作用

目的研究脑缺血大鼠缺血后适应模型中大脑皮质的ERK1/2通路表达特点及应用ERK1/2特异性抑制剂PD98059后对缺血后适应神经保护作用的影响,研究缺血后适应是否通过ERK1/2信号通路介导对急性缺血性脑梗死再灌注后的神经保护作用。方法将20只SD大鼠随机分为假手术组、缺血2h再灌注组、缺血2h后适应组以及PD98059+缺血2h后适应组(PD+2h后适应组),每组5只,用线栓法建立急性大脑中动脉闭塞的缺血性脑梗死模型,4组分别进行不同形式的实验。对比4组大鼠再灌注1h、24h的神经功能评分及再灌注24h后的梗死体积。每组另增加15只大鼠,分别于再灌注后2h、6h、24h留取缺血大脑皮质;Western blot检测再灌注2h、6h、24h后总T-ERK1/2、P-ERK1/2表达。结果 PD+2h后适应组与缺血2h再灌注组神经功能缺损评分高于缺血2h后适应组,脑梗死体积大于缺血2h后适应组。缺血后适应组再灌注2h、6h、24h后P-ERK1/2表达明显高于缺血2h再灌注组及PD+2h后适应组;以上表明,缺血后适应通过ERK1/2信号通路减轻大鼠缺血性脑损伤,应用P-ERK1/2的阻滞剂PD98059后,阻断了缺血后适应的脑保护作用。结论通过对本实验研究数据的分析后发现,缺血后适应对大鼠急性缺血性脑梗死具有神经保护作用,应用ERK1/2特异性抑制剂PD98059后,缺血后适应神经保护效应减弱,说明缺血后适应对急性缺血性脑梗死再灌注损伤的保护作用与MAPK/ERK信号通路具有深层次紧密关系。

The effect of ERK1/2 on the ischemic cortex of rats after ischemic postconditioning

Objective To investigate the expression of ERK1/2 in the ischemic cortex of rats after ischemic postconditioning and the effect of extracellular signal-regulated kinase(ERK) inhibitor PD98059 on neuroprotective effects of ischemic postconditioning.and to examine if ischemic postconditioning reduced acute ischemic cerebral infarction followed by reperfusion-induced neurological function and structure injury in rats by increasing the levels of ERK1/2.Methods Twenty (SD) rats were randomly assigned to sham-operated group,ischemic-reperfusion group,ischemic postconditioning group and PD98059+ ischemic postconditioning.We established acute middle cerebral artery occlusion (MCAO) models by using intraluminal suture method.We compared neurological deficit scores in the four groups at 1h and 24h after reperfusion.We compared infarct volume at the end of the 24-hour reperfusion.Furthermore,fifteen rats were added to each group and sacrificed at 2,6 and 24 hours after reperfusion,respectively.The phosphorylation of ERK1/2 and T-ERK1/2 in the ischemic cortex was measured by Western Blot at 2,6,24h after reperfusion.Results Neurological scoring and infarct volume in the group of postconditioning at 2 hours after infarction is minimum among the three groups.But the P-ERK 1/2 in the ischemic cortex of the ischemic postconditioning group were significantly increased at 2,6,24h after reperfusion than other two groups.Conclusion Through the analysis in this experiment,we found that ischemic postconditioning plays a positive role in neuroprotection,and PD98059 could inhibit the expression of ERK in ischemic cortex and decrease the neuroprotective effects,which suggests that MAPK/ERK may participate in neuroprotection of ischemic postconditioning after ischemia/reperfusion injury.